Chaperonin 10 (Cpn10), also known as early pregnancy factor (EPF) and heat shock protein 10 (Hsp10; HSPE1), functions as a molecular chaperone that facilitates the folding of cellular proteins. In particular, Cpn10 has been shown to form a complex with Chaperonin 60 (Cpn60) in the mitochondria of diverse cell types. This complex is responsible for the folding of polypeptides imported into the mitochondria, preventing peptide aggregation, and reactivating denatured proteins.
Cpn10 is thought to be involved in a number of other cellular processes in addition to its role in protein folding. For example, it has been suggested that Cpn10 regulates biological activities associated with pattern recognition receptors (PRRs). PRRs are responsible for initiating and driving immune responses upon recognition of specific ligands derived from pathogenic microorganisms known as “PAMPs” (pathogen-associated molecular patterns) (e.g. lipopeptides, glycolipids, nucleic acids) and/or host-derived ligands referred to as “DAMPs” (damage-associated molecular patterns) (e.g. nucleotides, nucleosides, DNA, proteins). For example, the binding of PAMPs to PRRs expressed by phagocytic cells (e.g. macrophages) has been shown to promote endocytosis and destruction of pathogens by the cell. Binding of PAMPs/DAMPs to PRRs also initiates cell signalling cascade(s) in various immune cells (e.g. macrophages, B lymphocytes and dendritic cells) culminating in the production and secretion of inflammatory mediators (e.g. cytokines, chemokines, reactive oxygen species etc).
Recent data suggests that Cpn10 down-regulates the production and secretion of pro-inflammatory molecules induced by PRR signalling. Cpn10 has also been implicated in the positive regulation of PRR-mediated production and secretion of anti-inflammatory molecules. The capacity of Cpn10 to modulate PRR signalling provides a means of treating a variety of diseases and disorders associated with activation of the immune system (e.g. inflammatory diseases). For example, administration of Cpn10 may be used to sequester ligands responsible for initiating PRR-signalling. This in turn suppresses the production and release of inflammatory mediators and thus inhibits immune activation and inflammation.
Despite the identification of Cpn10 as a suppressor of immune activation, there is a need for improved agents to prevent and/or treat inflammatory diseases and conditions. Ideally, such agents will be capable of binding to PRR ligands with increased affinity, thereby inhibiting the production and secretion of inflammatory molecules mediated by PRR-signalling.